Thromboembolic complications and abnormal bleeding are among the major complications of valvular heart disease, artificial heart valves, cardiopulmonary bypass, and left ventricular assist devices. The mechanisms by which platelets and the blood coagulation fibrinolytic system are activated in these conditions are incompletely understood. There is evidence indicating that both interaction of platelets with artificial surfaces or the diseased vasulature and the effects of fluid shear stress are involved in the activation of platelets. The studies proposed here are designed to examine in detail (1) the mechanisms by which well-controlled, uniform, laminar fluid shear stress (in the range that may be encountered in vivo) triggers platelet reactions (release of platelet granule constituents, platelet aggregation, platelet procoagulant availability) and causes platelet damage; (2) the effects of exposure of normal platelets to varying shear stresses (prolonged steady and repetitive short-term) on in vitro platelet function and in vivo platelet survival; (3) the effects of shear stress on "hypersensitive" platelets from patients with conditions associated with premature atherosclerotic disease; (4) the contribution of normal red blood cells (RBC) and RBC with decreased deformability on shear-induced platelet alterations; and (5) the effects of an abnormal, hyperviscous environment on shear-induced platelet alterations. The Couette rotational viscometer, because of its well-defined, uniform flow regime, appears to be a particularly suitable tool for these studies. The results of this investigation should provide important new basic information in regard to the response of platelets to fluid shear stress in vitro and in vivo and may aid in the development of a better rationale and specific stategies for prevention and treatment of thromboembolic and hemorrhagic complications associated with the conditions mentioned above.